MS risk in Vitamin D deficiency due to environmental factors and not due to genetic predisposition

Vitamin D deficiency increases multiple sclerosis(MS) risk due to environmental factors, not a genetic predisposition, suggests a new study.

A new study finds that the link between vitamin D deficiency and multiple sclerosis(MS)risk is determined by environmental factors rather than a genetic predisposition. There are no genetic risk factors associated with vitamin D in families with a history of multiple sclerosis (MS). The study has been published in the journal Brain and Behavior.

Vitamin D (VD) deficiency has been associated with multiple sclerosis (MS) and other autoimmune diseases (AIDs). However, the effect of the genetics of vitamin D (VD) on the risk of MS is subject to debate. The researchers conducted the study to focus on genes linked to the VD signalling pathway in families with MS. The evaluation of gene variants in all the members of families could contribute to additional knowledge on the information obtained from case-control studies that use nonrelated healthy people.

The hypothesis is that some people may carry genetic variations, or mutations, that impede communication of vitamin D messages to cells, or change the working of its pathway in the brain and spinal cord — the areas damaged by multiple sclerosis(MS).

Therefore the researchers examined several genes linked to vitamin D signalling within cases of familial MS. They looked at mutations in 94 individuals from 15 families who had at least two members with the disease.

The vitamin D signaling pathway consists of the biological routes by which this vitamin reaches our body — produced in the skin through exposure to sunlight or the small intestine through dietary choices — its activation, conversion to a hormone, uptake by cells, and its biological actions, which range from maintaining calcium and phosphorus levels to regulating immune responses.

They performed whole-exome next-generation sequencing on all individuals and analyzed variants of the DHCR7, CYP2R1, CYP3A4, CYP27A1, GC, CYP27B1, LRP2, CUBN, DAB2, FCGR, RXR, VDR, CYP24A1, and PDIA3 genes. They also studied PTH, FGF23, METTL1, METTL21B, and the role of the linkage disequilibrium block on the long arm of chromosome 12, through analysis of the CDK4, TSFM, AGAP2, and AVIL genes. The patients with MS, other AIDs and unaffected members from different family types were compared.

The study described the variants in the VD signalling pathway that appear in families with at least two patients with MS. Some infrequent variants were detected in these families, but no significant difference was observed between patients with MS and/or other AIDs and unaffected family members in the frequency of these variants. Variants previously associated with MS in the literature were not observed in these families or were distributed similarly in patients and unaffected family members.

The researchers concluded that the study of genes involved in the VD signalling pathway in families that include more than one patient with MS did not identify any variants that could explain the presence of the disease, suggesting that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. Our study also supports the analysis of cases and unaffected individuals within families in order to determine the influence of genetic factors, researchers said.

Based on the results, they concluded that vitamin D “could probably play a role in multiple sclerosis(MS) more as an environmental factor rather than as a genetic factor.”